This is a program to carry on a coordinated series of projects on the regulation and structure of the mammalian genome. We propose to continue to identify and characteriaze regulatory variants recognized as polymorphisms in intact mice, and to examine the relationship between altered gene expression studied at the protein and mRNA level and DNA sequence differences. One experimental focus is the Beta-glucuronidase system, where we propose to study the enzyme structure, its intracellular location, the genetic regulation of enzyme induction, isolate the gene in the form of recombinant DNA for DNA structural studies and as a probe, and examine the expression of Beta-glucuronidase chromatin. A second focus is a study of the genetics and molecular biology of a set of androgen responsive genes, including Beta-glucuronidase, other androgen-inducible sequences in kidney, and the set of secretory proteins from seminal vesicle. The third focus is an examination of the DNA sequence changes in these genetic variants and a set of selected genes to investigate the correlation between sequence changes and changes in gene regulation and to examine the stuctural basis for DNA sequence polymorphism. The work is supported by the development of a series of mouse genetic resources, including new congenic strains, wild-derived stocks and an extensive breeding program.